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学科主题: 基础医学
题名:
High-throughput cell-based screening reveals a role for ZNF131 as a repressor of ERalpha signaling
作者: Han, Xiao2; Guo, Jinhai2; Deng, Weiwei2; Zhang, Chenying2; Du, Peige1; Shi, Taiping2,3,4; Ma, Dalong2,3,4
刊名: BMC GENOMICS
发表日期: 2008-10-11
DOI: 10.1186/1471-2164-9-476
卷: 9, 期:0
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biotechnology & Applied Microbiology ; Genetics & Heredity
研究领域[WOS]: Biotechnology & Applied Microbiology ; Genetics & Heredity
关键词[WOS]: ESTROGEN-RECEPTOR-ALPHA ; HUMAN BREAST-CANCER ; MCF-7 CELLS ; TRANSCRIPTIONAL ACTIVITY ; EXPRESSION ; GENES ; PS2 ; PROLIFERATION ; CDNA ; BETA
英文摘要:

Background: Estrogen receptor alpha (ER alpha) is a transcription factor whose activity is affected by multiple regulatory cofactors. In an effort to identify the human genes involved in the regulation of ER alpha, we constructed a high-throughput, cell-based, functional screening platform by linking a response element (ERE) with a reporter gene. This allowed the cellular activity of ER alpha, in cells cotransfected with the candidate gene, to be quantified in the presence or absence of its cognate ligand E2.

Results: From a library of 570 human cDNA clones, we identified zinc finger protein 131 (ZNF131) as a repressor of ER alpha mediated transactivation. ZNF131 is a typical member of the BTB/POZ family of transcription factors, and shows both ubiquitous expression and a high degree of sequence conservation. The luciferase reporter gene assay revealed that ZNF131 inhibits ligand-dependent transactivation by ER alpha in a dose-dependent manner. Electrophoretic mobility shift assay clearly demonstrated that the interaction between ZNF131 and ERa interrupts or prevents ER alpha binding to the estrogen response element (ERE). In addition, ZNF131 was able to suppress the expression of pS2, an ER alpha target gene.

Conclusion: We suggest that the functional screening platform we constructed can be applied for high-throughput genomic screening candidate ER alpha-related genes. This in turn may provide new insights into the underlying molecular mechanisms of ER alpha regulation in mammalian cells.

语种: 英语
所属项目编号: 2006AA02A305
项目资助者: National High Technology Research and Development
WOS记录号: WOS:000260679600001
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58154
Appears in Collections:基础医学院_免疫学系_期刊论文

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作者单位: 1.Beihua Univ, Jilin 132013, Peoples R China
2.Chinese Natl Human Genome Ctr, Beijing 100176, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Lab Med Immunol, Beijing 100191, Peoples R China
4.Peking Univ, Ctr Human Dis Genom, Beijing 100191, Peoples R China

Recommended Citation:
Han, Xiao,Guo, Jinhai,Deng, Weiwei,et al. High-throughput cell-based screening reveals a role for ZNF131 as a repressor of ERalpha signaling[J]. BMC GENOMICS,2008,9(0).
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